We envision the epidermal chalone mechanism as an epinephrine-activated cascade of intra-epidermal molecular events whereby the feedback control of epidermal cell division is mediated via adenosine 3′,5′-monophosphate (cyclic AMP). Sutherland's first criterion of a cyclic AMP mediated event appears to have been satisfied in that isoproterenol (1 × 10-6M) produced a threefold (P < 0.001) rise in cyclic AMP level within three minutes in epidermal target tissue which was followed by inhibition of epidermal cell division. Since keratinocytes comprise approximately 95% of epidermal volume, we suggest that the majority of cyclic AMP measured was synthesized in keratinocytes.
Powell JA, Duell EA, Voorhees JJ. Beta Adrenergic Stimulation of Endogenous Epidermal Cyclic AMP Formation. Arch Dermatol. 1971;104(4):359–365. doi:10.1001/archderm.1971.04000220017004
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